Fannyhessea vaginae causing bacteraemia and vertebral osteomyelitis: first report of invasive disease in a male.

Introduction.Fannyhessea vaginae (formerly Atopobium vaginae) is an anaerobic organism commonly associated with female genital flora, with rare cases of invasive disease reported in females. Case report. We discuss the case of an 81-year-old male who presented with an acute history of back pain and signs of urinary tract infection in the context of intermittent self-urinary catheterisation. Multiple blood cultures grew Fannyhessea vaginae with a later finding of lumbar vertebral osteomyelitis as the cause of back pain. Treatment was commenced with ampicillin, later switched to ceftriaxone, with improvement of acute signs of infection. Conclusion. Gram-positive anaerobic organisms including Fannyhessea vaginae are possibly under-recognised causes of urinary tract particularly in older males. These bacteria may prove challenging to grow in standard protocols for urine culture; anaerobic or extended incubation could be considered particularly in complicated cases of urinary tract infection without an identifiable pathogen.

Niche suitability and spatial distribution patterns of anurans in a unique Ecoregion mosaic of Northern Pakistan.

The lack of information regarding biodiversity status hampers designing and implementing conservation strategies and achieving future targets. Northern Pakistan consists of a unique ecoregion mosaic which supports a myriad of environmental niches for anuran diversity in comparison to the deserts and xeric shrublands throughout the rest of the country. In order to study the niche suitability, species overlap and distribution patterns in Pakistan, we collected observational data for nine anuran species across several distinct ecoregions by surveying 87 randomly selected locations from 2016 to 2018 in Rawalpindi District and Islamabad Capital Territory. Our model showed that the precipitation of the warmest and coldest quarter, distance to rivers and vegetation were the greatest drivers of anuran distribution, expectedly indicating that the presence of humid forests and proximity to waterways greatly influences the habitable range of anurans in Pakistan. Sympatric overlap between species occurred at significantly higher density in tropical and subtropical coniferous forests than in other ecoregion types. We found species such as Minervarya spp., Hoplobatrachus tigerinus and Euphlyctis spp. preferred the lowlands in proximal, central and southern parts of the study area proximal to urban settlements, with little vegetation and higher average temperatures. Duttaphrynus bengalensis and D. stomaticus had scattered distributions throughout the study area with no clear preference for elevation. Sphaerotheca pashchima was patchily distributed in the midwestern extent of the study area as well as the foothills to the north. Microhyla nilphamariensis was widely distributed throughout the study area with a preference for both lowlands and montane terrain. Endemic frogs (Nanorana vicina and Allopaa hazarensis) were observed only in locations with higher elevations, higher density of streams and lower average temperatures as compared to the other seven species sampled. It is recommended to provide legal protection to amphibians of Pakistan, especially endemic species, through revision in the existing wildlife laws. We suggest studying the effectiveness of existing amphibian tunnels and corridors or designing new ones tailored to the needs of our species to prevent their local extinction due to ongoing or proposed urban development which might affect their dispersal and colonization.

Seroprevalence of SARS-CoV-2: Insights into the epidemiology of the pandemic.

AIM: This study aimed to assess the seroprevalence of SARS-CoV-2 and disease symptoms in Malakand, Pakistan. MATERIALS & METHOD: 623 samples with suspected SARS-CoV-2 were collected from different regions of Malakand and analyzed to detect SARS-CoV-2 IgG antibodies using ELISA. RESULTS: 306 (49.1%) 0 f 623 patients were anti-SARS-CoV-2 IgG reactive, with a higher prevalence in males (75%) than females (25%). In this study, we enrolled two groups, subjects working in a non-medical setting and subjects working in a medical setting. Clinical symptoms were statistically linked with SARS-CoV-2. Four weeks of follow-up analysis of IgG titers in health care workers showed an increase in IgG antibodies titer. CONCLUSION: This study gives insights into the community-based spread of SARS-CoV-2 infection, associated immunity, and herd immunity in the studied population. This study can provide insights to the government about early vaccination of this population as most of the population is not yet vaccinated.

LInezolid Monitoring to MInimise Toxicity (LIMMIT1): A multicentre retrospective review of patients receiving linezolid therapy and the impact of therapeutic drug monitoring.

BACKGROUND: Linezolid is a broad-spectrum antimicrobial with limited use due to toxicity. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM). METHODS: Patients administered linezolid between January 2017 and December 2019 were retrospectively reviewed. Data were collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between those who did and did not experience linezolid toxicity. A multivariable logistic regression model was constructed to identify any covariates that correlated with toxicity. RESULTS: Linezolid was administered to 1050 patients; of these, 381 did not meet the inclusion criteria and 47 were excluded as therapy ceased for non-toxicity reasons. There were 105 of 622 (16.9%) patients assessed to have linezolid toxicity. Patients who experienced toxicity displayed a higher baseline creatinine (96.5 µmol/L vs. 79 µmol/L; P = 0.025), lower baseline platelet count (225 × 109/L vs. 278.5 × 109/L; P = 0.002) and received a longer course (median 21 vs. 14 days; P < 0.001) than those who did not. Linezolid TDM was performed in 144 patients (23%). Multivariable logistic regression demonstrated that TDM-guided appropriate dose adjustment significantly reduced the odds of linezolid toxicity (aOR = 0.45; 95% CI 0.21-0.96; P = 0.038) and a treatment duration > 28 days was no longer significantly associated with toxicity. CONCLUSIONS: This study confirmed that linezolid treatment-limiting toxicity remains a problem and suggests that TDM-guided dose optimisation may reduce the risk of toxicity and facilitate prolonged courses beyond 28 days.

Lab protocol for investigating impacts of climate change on frogs.

We developed a method to investigate impacts of temperature (elevated) on breeding, growth and development in endemic frogs under laboratory conditions. The method provides details on housing and rearing of larvae, taking various important measurements and observing developmental deformities. The method could also be applied to rescue approach or head-start program for amphibian species experiencing climate change elsewhere in the world. • Rearing of larvae to investigate effects of temperature on larvae • Measurement of data on growth and development • Rescue/ head-start program.

Development and validation of an eDNA protocol for monitoring endemic Asian spiny frogs in the Himalayan region of Pakistan.

Wildlife monitoring programs are instrumental for the assessment of species, habitat status, and for the management of factors affecting them. This is particularly important for species found in freshwater ecosystems, such as amphibians, as they have higher estimated extinction rates than terrestrial species. We developed and validated two species-specific environmental DNA (eDNA) protocols and applied them in the field to detect the Hazara Torrent Frog (Allopaa hazarensis) and Murree Hills Frog (Nanorana vicina). Additionally, we compared eDNA surveys with visual encounter surveys and estimated site occupancy. eDNA surveys resulted in higher occurrence probabilities for both A. hazarensis and N. vicina than for visual encounter surveys. Detection probability using eDNA was greater for both species, particularly for A. hazarensis. The top-ranked detection model for visual encounter surveys included effects of both year and temperature on both species, and the top-ranked occupancy model included effects of elevation and year. The top-ranked detection model for eDNA data was the null model, and the top-ranked occupancy model included effects of elevation, year, and wetland type. To our knowledge, this is the first time an eDNA survey has been used to monitor amphibian species in the Himalayan region.

Cerebral Salt-Wasting Syndrome in a Patient With Active Pulmonary Tuberculosis.

A 37-year-old female with a medical history of recently diagnosed active pulmonary tuberculosis and a new intracranial lesion presented with altered mental status, nausea, and vomiting for two days. An initial physical examination revealed that the patient was euvolemic. Laboratory findings revealed a serum sodium concentration of 105 mEq/L. During her admission, she was initially managed with lactated ringer solution in the emergency department, followed by 3% normal saline in the intensive care unit, and, eventually, on oral sodium chloride and fluid restriction on discharge. Once she was stabilized, she had episodes of dizziness, and concerns were raised about the salt-wasting syndrome.

Movement Paradigm for Hazara Torrent Frog Allopaahazarensis and Murree Hills Frog Nanoranavicina (Anura: Dicroglossidae).

Endemic anurans are particularly vulnerable to environmental changes, and are susceptible to population declines because of their restricted distribution ranges. The Murree Hills Frog Nanoranavicina and Hazara Torrent Frog Allopaahazarensis are associated with the torrential streams and nearby clear water pools in subtropical chir pine forest and other forest types, at elevations higher than 1000 m in Pakistan. In this study, we have provided data on the extent of movement of these frog species for the first time. We installed radio transmitters on a total of 13 Murree Hills Frogs and 13 Hazara Torrent Frogs during eight consecutive days in September 2017 and 2018. Our results showed that these frogs did not move long distances along the stream or away from the stream into the forest. All the radio-tracked frogs showed movement of < 3 m. We found a significant differences only in the distance moved by Murree Hills Frogs between the two years studied. Based on our findings, we propose a movement paradigm that focuses on conservation implications for these endemic frogs.

Amphibian fauna of Pakistan with notes on future prospects of research and conservation.

Research on amphibians and their conservation have gained worldwide attention, as the group includes the highest number of threatened and Data Deficient species when compared to other vertebrates. However, amphibians have long been neglected in wildlife conservation, management decisions, policy making, and research agendas in Pakistan. In this paper, an annotated checklist of the 21 amphibian species of Pakistan, a key to their identification, and detailed discussions on variation in species, including the genera Minervarya and Sphaerotheca, are provided. We found a statistically significant difference in the morphometric measurements of males but non-significant difference in the females of the two forms (rusty dorsum and dotted dorsum) of S.maskeyi. Some genera, such as Microhyla, Uperodon, Minervarya, Allopaa, Chrysopaa, Euphlyctis, Nanorana, and Sphaerotheca, in Pakistan are in need of additional data for molecular and morphological comparisons with taxa in other South Asian countries. The predicaments of amphibian research in Pakistan are discussed, gaps identified, and suggestions are made. Although the occurrence of chytrid fungus in Pakistan is predicted of low likelihood, a lack of data merits studying the prevalence of the fungus, particularly in the northern regions of the country which exhibit complex and dynamic ecosystems. It is recommended that systematic and coordinated surveys are conducted throughout the country to build a database of species occurrences and distributions. Additionally, the monitoring of wild populations and threat mitigation, as well as appropriate legislation, are suggested as long-term measures. By adopting an inclusive wildlife conservation approach in Pakistan, amphibians could be integrated into wildlife conservation and management efforts.

An insight into molecular taxonomy of bufonids, microhylids, and dicroglossid frogs: First genetic records from Pakistan.

The current study was focused on documentation of amphibian assemblage in North Punjab and Islamabad Capital Territory, Pakistan, by using mitochondrial gene sequences of 16S rRNA. Our study entailed 37% of the known amphibian species of the country. We provided a phylogenetic analysis based on 74 newly generated mitochondrial 16S rRNAs from nine species of genus Microlyla, Duttaphrynus, Allopaa, Nanorana, Sphaerotheca, Minervarya, Hoplobatrachus, and Euphlyctis. We employed the maximum-likelihood inference and Bayesian analysis to assess the taxonomic status of the samples obtained from Pakistan, with respect to other congeneric species from surrounding regions. Our findings confirmed the taxonomic status of South Asian anuran species Duttaphrynus stomaticus, Duttaphrynus melanostictus, Microhyla nilphamariensis, Allopaa hazarensis, Nanorana vicina, Sphaerotheca maskeyi (synonym: S. pashchima), Minervarya pierrei, Hoplobatrachus tigerinus, and Euphlyctis kalasgramensis in Pakistan. We have reported new country records of genus Minervarya ( M. pierrei). Minervarya pierrei was previously misidentified as Fejervarya limnocharis, due to dearth of genetic information. We provided the first genetic records of our endemic species N. vicina. The results revealed the taxonomic placement of N. vicina with respect to its congeners and validated the taxonomic status of N. vicina from its type locality (Murree) for the first time. The findings of the present study also indicated the paraphyletic relationship of A.- hazarensis with Nanorana species. So, based on our phylogenetic inferences, morphological characters, and habitat preferences, validity of generic status of A. hazarensis is undecided. As our data were not enough to resolve this issue, we suggest sequencing of additional mitochondrial and nuclear genes in the future studies to get a better resolution. We recommend carrying out extensive surveys throughout the country for proper scientific documentation of amphibians of Pakistan. Many new species, some of them might be endemic to Pakistan, are expected to be discovered, and taxonomic status of other species would be resolved.

Reactive Hypoglycemia From Metformin Immediate-Release Monotherapy Resolved by a Switch to Metformin Extended-Release: Conceptualizing Their Concentration-Time Curves.

Metformin rarely, if ever, causes hypoglycemia when it is used as labeled. A 55-year-old woman presented to the medicine ward with an altered level of consciousness. She had been reviewed in an outpatient department three days earlier and prescribed 500 mg two times per day of metformin immediate-release (Met IR) for newly diagnosed type 2 diabetes mellitus (T2DM), to which she had been adherent; however, she had been experiencing intermittent episodes of hypoglycemia after taking the medication prescribed to treat her T2DM. On physical examination, she was diaphoretic and disoriented but responsive to sensory stimuli. In the ward, she received 25 ml of intravenous dextrose as the initial blood glucose reading was low at 54 mg/dl, and 4 ounces of apple juice additionally two hours later as her blood glucose level fell below 70 mg/dl again. She was no longer hypoglycemic a few hours later, and there was a significant neurological improvement. The remainder of the laboratory results, including serum renal and liver function tests, were normal. Met IR was discontinued, and metformin extended-release (Met XR) 500 mg/day was initiated at discharge. The patient's hypoglycemic episodes resolved within days after the initiation of Met XR. Hypoglycemia is rarely associated with accidental or suicidal overdose of metformin, metabolic dysfunction (e.g., renal insufficiency), exercise, missed meal, acute illness, or the initiation of additional antidiabetic medication. Albeit even uncommon, metformin-associated hypoglycemia may occur with no obvious trigger. In this context, we determine to what extent Met IR may contribute to the development of hypoglycemia in an individual case, but also that the risk could be mitigated by a switch to Met XR. In a preferred embodiment, the Met XR dosage form can be administered once a day, ideally with or after a meal, preferably with or after the evening meal, and it provides therapeutic levels of the drug throughout the day with peak plasma levels being obtained between four to eight hours after the administration (Tmax).

Myeloma Cast Nephropathy and COVID-19: A Case Report of Multiple Myeloma Presenting as Acute Kidney Injury in the Setting of COVID-19.

A 64-year-old African American male presented to the emergency department with subacute low back pain for two weeks and decreased urine output. He was found to have a potassium level of 9.2 mmol/L and was uremic with a creatinine level of 28.5 mg/dL and blood urea nitrogen (BUN) level of 201 mg/dL. He also tested positive for COVID-19. He was then started on continuous renal replacement therapy (CRRT). His urinalysis showed more than 500 mg/dL of protein. A workup for multiple myeloma was also conducted, and urine protein electrophoresis test was positive for free lambda light chains with a level of 17,700 mg/L and free kappa light chains with a level of 88.30 mg/L with a kappa:lambda free light chain ratio of 0.005. Additionally, serum Bence Jones protein level was elevated at 240 mg/dL, and serum beta-2 microglobulin level was elevated at 31.41 mg/L. An immunoglobulin (Ig) panel also showed low levels of IgG, IgA, and IgM. Kidney biopsy for this patient showed definite cast nephropathy and minimal chronic changes, with only one of over 20 glomeruli sclerosed and minimal interstitial deposits. The patient was started on chemotherapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD).

Notalgia Paresthetica: Cervical Spine Disease and Neuropathic Pruritus.

Notalgia paresthetica (NP) is a dermatologic condition with predominant, primarily left unilateral pruritus and hyperpigmentation that typically occurs on the upper and middle back. The etiology remains largely elusive. A 57-year-old female with a history of neck pain presented with refractory NP since six months. Through diagnostic x-ray, cervical degenerative changes were discovered at the C5-C6 level, and she was prescribed a course of cervical traction. The cervical theory of NP is presented and is supported with x-ray findings in this case.

A Unique Case of Valacyclovir Toxicity and Pseudobulbar Affect in a Patient On Peritoneal Dialysis.

There are a few cases of valacyclovir-associated neurotoxicity (VAN) reported. This case report documents a case of a 55-year-old male presenting with emotional lability or pseudobulbar affect as the predominant or sole manifestation of VAN. A failure to adjust valacyclovir's dose for herpes simplex infection in the setting of dialysis-dependent end-stage renal disease (ESRD) preceded VAN in this patient. The patient presented with involuntary and uncontrollable outbursts of emotion. Computerized tomography (CT) scan identified no underlying cause. A complete neurological examination with cognitive assessment was performed, with no abnormalities. He benefited from the use of aggressive peritoneal dialysis (PD) that was employed to enhance valacyclovir's clearance in this case of intractable VAN. On discharge, the patient was back to baseline mental function. Traumatic brain injury, neoplasm, vascular lesions, metabolic abnormality, neurological disease, herpetic encephalitis, and disorders of mood were ruled out. This led to the hypothesis of encephalopathy due to valacyclovir intoxication. Given that the clinical manifestations were related to ESRD, a dose-adjustment of valacyclovir is imperative in the setting of ESRD to prevent VAN. Our case presents important clinical variations. Firstly, our patient demonstrates that VAN may present with no focal neurological impairment, but pseudobulbar affect. Secondly, aggressive PD was useful in this case for the treatment of VAN as opposed to hemodialysis. We believe that it cleared valacyclovir resulting in the resolution of symptoms.

Rise in temperature causes decreased fitness and higher extinction risks in endemic frogs at high altitude forested wetlands in northern Pakistan.

The larvae of some amphibian species grow and develop more slowly at lower temperature and attain larger body size at the end of metamorphosis, but this is not true for all amphibians. We have for the first time provided empirical data by using a combination of field and lab-based studies with a robust sample size (360 adults, 1000 tadpoles) for Hazara Torrent Frog (Allopaa hazarensis) and Murree Hills Frog (Nanorana vicina). In this study, we examined how tadpoles responded to different temperatures through metamorphosis, body size, developmental complications or deformities, fitness and survival. We found that the tadpoles of A. hazarensis and N. vicina showed the same response to elevated temperatures under laboratory conditions including faster metamorphosis, reduction in the body size, more frequent developmental complications or deformities such as edema and tail kinks, lower fitness and higher mortality at elevated temperatures (>26 °C). The comparison of thermal sensitivity between the two species showed that N. vicina was more sensitive to higher temperatures. Pakistan has been experiencing changes in climatic patterns, and the ecosystems in northern Pakistan are losing biodiversity due to increasing temperature, frequency of drought and intensity of floods. It is feared that these frogs may experience local extinction in future. Our findings contribute to filling the information gap regarding impacts of temperature increase on biodiversity of high altitude forested montane ecosystems and is an important contribution to future studies associating biodiversity and climate change.

Tuberculosis-Induced Bronchiectasis Complicated by Recurrent Respiratory Tract Infections and Renal Amyloidosis: A Classic Revisited.

In this case, a young male patient with a past medical history of adequately treated pulmonary tuberculosis (TB), presented with pedal edema, proteinuria, and evidence of bilaterally enlarged kidneys on renal ultrasound, raising suspicion of renal amyloidosis. Cough, expectoration, severe dyspnea, and high-resolution computed tomographic changes of dilated bronchi paralleled evidence of bronchiectasis exacerbated by perpetual bacterial infection. In view of the laboratory findings and imaging studies, a renal biopsy was done, and it supported the diagnosis of secondary amyloidosis in the kidneys. Clearly, TB infection, although treated, had exerted a multifaceted effect, and it ran a downward spiral from there: the simultaneous occurrence of bronchiectasis and recurrent respiratory tract infections, renal amyloidosis, nephrotic syndrome and an inevitable end-stage renal failure in just the third decade of life. It makes sense then, to use adjuvant steroid therapy as complementing traditional TB therapy to combat the destructive and fibrosing properties of pulmonary TB.

Laparoscopy: A Better Approach for Perforated Duodenal Ulcer.

Background Laparoscopic surgery is becoming the gold standard for most abdominal surgeries in recent times. Laparoscopic repair of perforated duodenal ulcer (PDU), however, is still an area of debate. The purpose of this study was to evaluate the safety and efficacy of laparoscopic repair of PDU versus open repair. Methods In this cross-sectional study, patients were consecutively sampled. Out of 101 patients with clinically diagnosed PDU, 36 patients underwent laparoscopic Graham patch repair and 65 underwent open Graham patch repair in a tertiary care academic hospital. Open repair was via upper midline incision, and laparoscopic repair by the three-port technique. The following stages were calculated: operative time, duration of postoperative analgesia, time taken to mobilize, and patient length of stay after the operation. Results The mean operative time was somewhat longer in the laparoscopy group compared to the open repair group (74.01 vs 56.17 minutes, respectively). Mean postoperative analgesia requirement, time taken to mobilize, and hospital stay were significantly shorter after laparoscopy than after open repair (1.21 days, 9.32 hours, and 3.12 days vs 3.83 days, 16.20 hours, and 4.85 days, respectively). Three patients (8%) in the laparoscopy group and 35 (54%) in the open repair group had postoperative complications. Conclusions Laparoscopic repair of PDU is a safe approach and better than open repair in terms of operative time with the right level of expertise only, postoperative analgesia requirement, mobilization, duration of hospital stay, and incidence of postoperative respiratory and wound complications.

The tadpoles of Murree Hills Frog Nanorana vicina (Anura: Dicroglossidae).

The genus Nanorana, also called Yunnan Slow Frogs (Frank Ramus 1995), belongs to the family Dicroglossidae. Murree Hills Frog N. vicina, is an endemic species of Southeast Asian uplands in Pakistan and India and was first reported by Stoliczka (1872) from Murree, Punjab Province, Pakistan. Later Rais et al. (2014) recaptured it from its type locality and described morphology of one juvenile female and one adult male. The species is listed as Least Concern in IUCN Red List of Threatened Species while the EDGE (Evolutionarily Distinct and Globally Endangered) score is 2.64. In Pakistan, it is reported from brook water springs and streams of Murree, Galiat (North Punjab), Ayubia (Khyber Pakhtunkhwa), and parts of Azad Jammu and Kashmir (Rais et al. 2014). Although the adult form has been characterized (Khan 2006; Rais et al. 2014), the morphology of the tadpoles have not yet been described. The current study aimed to describe external morphology and morphometry of tadpoles of N. vicina.

Overwhelming COVID-19 Sepsis in a Patient With Idiopathic Pulmonary Fibrosis.

The new disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was dubbed coronavirus disease 2019 (COVID-19) by the World Health Organization and declared a pandemic. Initially thought to be a pathogen that primarily attacks the lungs, SARS-CoV-2 has turned out to be a much more formidable foe impacting almost every organ and system aggressively. I report the case of a 60-year-old man who came to the ED due to symptoms of high fever, headache, mild confusion, dry cough and exacerbated dyspnea since the last 24 hours. He had a history of idiopathic pulmonary fibrosis (IPF) and was undergoing treatment with antifibrotic medication. Apart from IPF, he had no other comorbid. He acquired SARS-CoV-2 infection by close contact and infection deteriorated into pneumonia and septic shock. Complete blood count showed white blood cells at 3.3×103/µL and platelets at 71×103/µL; lymphocyte count was low. Arterial blood gases revealed metabolic acidosis. Definitive diagnosis was by a positive real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens, and high-resolution computed tomography (HRCT) finding of new-onset ground-glass opacities on the very first day of admission that was the presenting day. The patient became unresponsive and died overnight. As numbers of COVID-19 show an uprise, this case highlights that IPF patients with relatively advanced age need to exercise extra caution because they are at high risk for developing overwhelming COVID-19-linked sepsis, which may be fatal.