Male Infertility: Causes and Management at a Tertiary Care Center in India.

Background Infertility and problems of impaired fecundity have been a concern through the ages and are also considerable clinical problems today, affecting many couples worldwide. Most infertility cases are primarily attributed to male factors, which play a significant role. Additionally, a substantial number of these patients exhibit suboptimal sperm parameters. The study is mainly designed for individual intervention and outcome. We aim to evaluate the demographics, etiology, utilization of treatments, and outcomes of males undergoing infertility treatment. Methodology We retrospectively enrolled infertile couples from January 2021 to March 2023, covering the past two years. All patients were evaluated and investigated per the study protocol to identify the cause of infertility. Results Two thousand three hundred forty-eight males were enrolled in the study, of whom 1,484 (63%) were found to have a standard semen analysis. A total of 868 (37%) had abnormal semen parameters. Two hundred and seventy-two (12%) patients completed the evaluation. All parameters, except for hypospermia, displayed lower percentages of motility compared to normozospermia. All semen parameters, except for hypospermia, showed a significantly lower normal morphology in comparison to normozospermia. This reduction increased by 10% for each year of age increment. Conclusions The study concluded by following a protocol for evaluating male patients. If an abnormal sperm parameter is identified before considering intracytoplasmic sperm injection (ICSI), it is recommended to conduct at least karyotyping and microdeletion analysis on the Y-chromosome's q arm.

Elevated insulin growth factor-1 in dentate gyrus induces cognitive deficits in pre-term newborns.

Prematurely born infants are deprived of maternal hormones and cared for in the stressful environment of Neonatal Intensive Care Units (NICUs). They suffer from long-lasting deficits in learning and memory. Here, we show that prematurity and associated neonatal stress disrupt dentate gyrus (DG) development and induce long-term cognitive deficits and that these effects are mediated by insulin growth factor-1 (IGF1). Nonmaternal care of premature rabbits increased the number of granule cells and interneurons and reduced neurogenesis, suggesting accelerated premature maturation of DG. However, the density of glutamatergic synapses, mature dendritic spines, and synaptic transmission were reduced in preterm kits compared with full-term controls, indicating that premature synaptic maturation was abnormal. These findings were consistent with cognitive deficits observed in premature rabbits and appeared to be driven by transcriptomic changes in the granule cells. Preterm kits displayed reduced weight, elevated serum cortisol and growth hormone, and higher IGF1 expression in the liver and DG relative to full-term controls. Importantly, blocking IGF-1 receptor in premature kits restored cognitive deficits, increased the density of glutamatergic puncta, and rescued NR2B and PSD95 levels in the DG. Hence, IGF1 inhibition alleviates prematurity-induced cognitive dysfunction and synaptic changes in the DG through modulation of NR2B and PSD95. The study identifies a novel strategy to potentially rescue DG maldevelopment and cognitive dysfunction in premature infants under stress in NICUs.

Sustained response on sequential anti-FGFR therapy in metastatic gall bladder cancer: a case report and literature review.

PURPOSE: Advanced gall bladder cancer (GBC) is an aggressive disease, and there is no consensus on treatment options beyond first-line chemotherapy. We report a case of an elderly male with FGFR2-altered advanced adenocarcinoma of the gallbladder who failed two prior lines of chemotherapy but had sustained response and stable disease on sequential FGFR-directed targeted therapy. DESIGN: We describe a case of FGFR2-altered metastatic adenocarcinoma of the gallbladder who failed two prior lines of chemotherapy. The treatment was based on comprehensive genomic profiling when the patient was found to have FGFR2 single amino acid mutation (S252W) in one of his tissue samples. A novel therapeutic regimen with sequential anti-FGFR tyrosine kinase inhibitors was later initiated. RESULT: The patient tolerated the sequential targeted therapy very well and had a sustained response and stable disease. He had an overall survival of nearly five years. Unfortunately, GBC is an aggressive disease, and there is no consensus on treatment options beyond first-line chemotherapy. CONCLUSION: Through this patient, we demonstrate that advanced-metastatic GBC with FGFR alterations can be maintained on anti-FGFR therapy for prolonged periods of time, with improved survival. Therefore, we endorse the need for comprehensive genomic profiling in advanced-metastatic GBC and the need to study the role of FGFR inhibitors as a viable treatment option in these patients.

Shh activation restores interneurons and cognitive function in newborns with intraventricular haemorrhage.

Premature infants with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) suffer from neurobehavioural deficits as they enter childhood and adolescence. Yet the underlying mechanisms remain unclear. Impaired development and function of interneurons contribute to neuropsychiatric disorders. Therefore, we hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Because Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signalling might restore neurogenesis, cortical interneuron population, and neurobehavioural function in premature newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH and autopsy samples from human preterm infants. We compared premature newborns with and without IVH for intraneuronal progenitors, cortical interneurons, transcription factors regulating neurogenesis, single-cell transcriptome of medial ganglionic eminence and neurobehavioural functions. We treated premature rabbit kits with adenovirus expressing Sonic Hedgehog (Ad-Shh) or green fluorescence protein gene to determine the effect of Sonic Hedgehog activation on the interneuron production, cortical interneuron population and neurobehaviour. We discovered that IVH reduced the number of Nkx2.1+ and Dlx2+ progenitors in the medial ganglionic eminence of both humans and rabbits by attenuating their proliferation and inducing apoptosis. Moreover, IVH decreased the population of parvalbumin+ and somatostatin+ neurons in the frontal cortex of both preterm infants and kits relative to controls. Sonic Hedgehog expression and the downstream transcription factors, including Nkx2.1, Mash1, Lhx6 and Sox6, were also reduced in kits with IVH. Consistent with these findings, single-cell transcriptomic analyses of medial ganglionic eminence identified a distinct subpopulation of cells exhibiting perturbation in genes regulating neurogenesis, ciliogenesis, mitochondrial function and MAPK signalling in rabbits with IVH. More importantly, restoration of Sonic Hedgehog level by Ad-Shh treatment ameliorated neurogenesis, cortical interneuron population and neurobehavioural function in kits with IVH. Additionally, Sonic Hedgehog activation alleviated IVH-induced inflammation and several transcriptomic changes in the medial ganglionic eminence. Taken together, IVH reduced intraneuronal production and cortical interneuron population by downregulating Sonic Hedgehog signalling in both preterm rabbits and humans. Notably, activation of Sonic Hedgehog signalling restored interneuron neurogenesis, cortical interneurons and cognitive function in rabbit kits with IVH. These findings highlight disruption in cortical interneurons in IVH and identify a novel therapeutic strategy to restore cortical interneurons and cognitive function in infants with IVH. These studies can accelerate the development of new therapies to enhance the neurodevelopmental outcome of survivors with IVH.

Paradigm shift from palliation to cure in metastatic microsatellite high colorectal carcinoma with immune checkpoint inhibitors.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed malignancies worldwide with a high mortality rate. CRC is often plagued with significant treatment-related morbidity and mortality, and metastatic progression is common. With the advent of immunotherapy, inoperable and advanced cancers have shown favorable response. Immunotherapy has paved the way for survival of all those with advanced metastatic disease whose treatment was limited to palliative care. We explore the case of a 28-year-old female with advanced metastatic CRC refractory to chemotherapy and targeted therapy, managed with PD-1 inhibitor with complete clinical and pathological response in a relatively short period of time. The notion of upfront immunotherapy for advanced metastatic CRC with microsatellite instability is definitely reinforced by the favorable response seen in our case, and we hope that these findings would help reduce the dependence on chemotherapy as the mainstay therapeutic for advanced CRC.

Oral mucositis-case series of a rare adverse effect associated with immunotherapy.

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, act by inhibiting programmed death-1 and activating the T cells against cancer. An imbalance in this immune response, however, could lead to immune-related adverse events (irAEs) involving multiple organs like rash, fatigue, hypo and hyperthyroidism, pneumonitis, hepatitis, and colitis, among others. Oral irAEs are not uncommon among immune checkpoint inhibitors which include xerostomia, dysgeusia, and lichenoid reactions; however, oral mucositis is rarely seen or reported in patients receiving PD-1 inhibitors. We present 3 cases of this rare complication in varying grades of severity. The patients were managed with steroids, either topical or systemic, depending on the severity of the lesions with either postponement or withholding therapy due to toxicity. Through this article, we hope to bring to light this overlooked and underdiagnosed oral adverse event associated with the use of immunotherapy and various treatment options for its management.

The role of stimulation protocol, number of oocytes retrieved with respect to follicular fluid oxidative stress and IVF outcome.

The study was conducted on a population of 203 women attending the IVF clinic, Ahmedabad, India, to explore the role of stimulation protocol and the number of oocytes retrieved on oxidative stress in follicular fluid and IVF outcome. Follicular fluid was collected during ovum pick-up to determine the oxidative stress markers: superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), total thiols (TT), l-ascorbic acid (AA), total protein, glutathione S-transferase (GST) and glutathione reductase (GRD). The average number of oocytes retrieved was significantly higher in the women receiving a long GnRH agonist protocol compared to GnRH antagonist protocol while the percentage of women with positive IVF outcome was lower in the long agonist protocol. The level of total thiols was significantly lower in the group of women administered a short agonist protocol. The proportion of ETs carried out and positive IVF outcome were higher following retrieval of an intermediate number of oocytes (6-10 oocytes) compared to a lower (0-5 oocytes) and higher (>10 oocytes) number. Mean glutathione reductase (GRD) activity in follicular fluid was significantly elevated in the intermediate (6-10) and higher (>10) oocyte retrieval groups compared to the lower oocyte retrieval group. Positive IVF outcomes were highest when oocyte retrieval was in the range of 6-10 oocytes, and the level of MDA was lower (1.76 ± 0.13 nmol/ml) as compared to 0-5 and >10 oocytes retrieved groups.

Arthroscopic ACL reconstruction using fixed suspensory device versus adjustable suspensory device for femoral side graft fixation: What are the outcomes?

INTRODUCTION: The aim of the study was to evaluate the outcomes of Arthroscopic ACL Reconstruction using Fixed suspensory device and Adjustable suspensory device for femoral side graft fixation. MATERIAL AND METHODS: We conducted a prospective study of sixty two patients with ACL deficient knees treated with arthroscopic ACL reconstruction. Consecutively patients were operated with fixed loop and adjustable loop suspensory devices for femoral side graft fixation and no randomization was done. RESULTS: Functional assessment was performed with VAS score, IKDC score and Lyshom score before and after surgery with ACL reconstruction. The postoperative Lyshom score in fixed loop group and adjustable loop group was 94.23 and 94.32 respectively. The IKDC score in fixed group and adjustable group was 92.03 and 92.16 respectively. VAS in fixed loop group improved from score of 5-3, while in adjustable loop group from score of 4-3. There was significant improvement in stability of knee assessed by Lachman's test, anterior drawer test, and Pivot shiff's test and both methods of fixation provide stability to knee. The complications included; restriction of terminal flexion in 12 patients: 6 in each group. There was no implant breakage in both groups. CONCLUSION: Arthroscopic ACL reconstruction using fixed loop and adjustable loop suspensory devices are equally effective fixation methods.

Two cases of Dieulafoy lesions of the bronchus with novel comorbid associations and endobronchial ablative management.

RATIONALE: Dieulafoy lesions are aberrantly large submucosal arteries most frequently associated with gastrointestinal hemorrhage. They are rarely identified in the bronchial submucosa and can cause massive hemoptysis. PATIENT CONCERNS: We present three episodes of massive hemoptysis in two patients, the first with comorbid Alagille syndrome including multiple cardiac and pulmonary vascular abnormalities and the second with thyroid cancer metastatic to the mediastinum. DIAGNOSES: All episodes were due to Dieulafoy lesions of the bronchus based on bronchoscopic appearance. INTERVENTIONS: Bronchoscopic ablation using Nd:YAP laser was attempted both patients. OUTCOMES: Nd:YAP laser successfully ablated the Dieulafoy lesion in the first case with long-term relief from recurrent hemoptysis. The first episode in the second patient responded to bronchial artery embolization; laser ablation of a different Dieulafoy lesion responsible for the second episode was unsuccessful but additional bronchial artery embolization has provided relief from further episodes. LESSONS: Bronchoscopic ablation of Dieulafoy lesions of the bronchus can provide durable relief from recurrent symptoms. Clinical and anatomical features should be considered carefully before intervention, which should only be attempted by experienced operators with appropriate ancillary support available.

Role of environmental factors & oxidative stress with respect to in vitro fertilization outcome.

Background & objectives: Oxidative stress, lifestyle factors as also exposure to certain environmental factors are known to affect the fertility status in human beings. The aim of this study was to evaluate the role of OS and lifestyle and environmental factors affecting IVF outcome. Methods: A total of 253 couples were included, and biological samples such as blood, follicular fluid (FF), cumulus cells and semen were collected. Relevant biochemical parameters and metals namely lead (Pb), cadmium (Cd), copper (Cu) and zinc (Zn) were determined in the biological samples. ß-human chorionic gonadotropin levels ≥100 IU/l were considered to predict viable pregnancy on the 15th day of embryo transfer (ET). Results: The mean body mass index (BMI) was significantly lower in females with positive IVF outcome compared to those with negative outcome. Couples residing in the residential area showed more percentage of positive IVF outcomes as compared to couples residing in industrial/agricultural area. FF Zn level was significantly higher (P<0.001) among the females' participants who have undergone ET as compared to those who have not undergone ET. FF MDA and serum Cu levels were significantly higher (P<0.05) in the female participants with negative IVF outcome as compared to positive IVF outcome. Logistic regression revealed that maternal BMI (P=0.034) and FF MDA level (P=0.047) were significantly associated with the IVF outcome. Interpretation & conclusions: The success rate of IVF was about 31.8 per cent, and BMI was significantly lower in females with positive outcome. The higher levels of MDA in FF and SP might have a negative impact on IVF outcome, higher Zn level in SP, FF and serum might have a positive role in embryo transfer as well as IVF outcome. The role of stress management and nutrition supplementation during the IVF treatment may be explored.

Simultaneous bilateral shoulder and bilateral central acetabular fracture dislocation: What to do?

Musculoskeletal injuries following seizures have a high morbidity and mortality. These injuries are often missed and the diagnosis is delayed due to a lack of clinical suspicion and appropriate investigations.We report a case of 72 years old male with simultaneous bilateral central acetabular fracture dislocation and bilateral posterior shoulder fracture dislocation secondary to an epileptic seizure. Present study high- lights the significance of clinical suspicion and clinico-radiological evaluation for diagnosis of a rare injury following episode of seizures. Simultaneous fracture dislocation of all four limbs treated with a holistic approach can lead to a good functional recovery. Surgical management with open reduction and internal fixation is preferred and replacement arthroplasty should be reserved for cases with implant failure and elderly patients.